Dose-response Analysis of Aripiprazole in Patients with Schizophrenia in Taiwan

Overview

Journal Ther Adv Psychopharmacol

Specialty Psychiatry

Date 2022 Aug 4

PMID 35923249

Authors

Yun Tien

Hsiang-Ping Huang

Ding-Lieh Liao

Shang-Chien Huang

Affiliations

Soon will be listed here.

Abstract

Background: Aripiprazole is a third-generation antipsychotic agent with acceptable efficacy and a good safety profile. Previous studies have indicated the therapeutic serum concentration of aripiprazole to be 100 to 350 ng/ml; however, most of these studies examined a Western population. Patients with schizophrenia from Tungs' Taichung MetroHarbor Hospital in central Taiwan were recruited to analyze the dose-response relationship of aripiprazole in the Chinese population.

Objective: We aimed to investigate whether a serum concentration of aripiprazole higher than the current suggested range leads to higher response rates.

Design: A prospective cohort study was designed to investigate the response rates in different studied cohorts grouped by serum concentration of aripiprazole.

Data Sources And Methods: Data of 64 patients who presented to a single medical center in central Taiwan and who received therapeutic drug monitoring (TDM) were obtained. Serum concentrations of aripiprazole were correlated with the clinical response of patients by using the Clinical Global Impressions (CGI) scores.

Results: The mean concentration of aripiprazole was 432.1 ± 275.1 ng/ml in the study cohort. Among the much-improved patients, the mean serum concentration of aripiprazole was 494 ± 273 ng/ml (25th-75th percentiles 264-666 ng/ml), which was higher than the current recommended therapeutic target of 100-350 ng/ml for aripiprazole. The response rate in the severe group (baseline CGI score of 6 or 7) was significantly higher than in the moderate group (baseline CGI score of 4 or 5; 86.7% 55.9%, = 0.007).

Conclusion: A significantly higher response rate was observed in the study cohort with serum aripiprazole concentrations over 300 ng/ml. Therefore, dosing higher than the current recommended range may potentially improve the treatment efficacy in the Chinese population. Because the serum concentration varies among patients due to multiple intrinsic and extrinsic factors, TDM, especially in outpatients, is recommended if the clinical response is limited.

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References

McEvoy J, Daniel D, Carson Jr W, McQuade R, Marcus R . A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. J Psychiatr Res. 2007; 41(11):895-905. DOI: 10.1016/j.jpsychires.2007.05.002. View

Preda A, Shapiro B . A safety evaluation of aripiprazole in the treatment of schizophrenia. Expert Opin Drug Saf. 2020; 19(12):1529-1538. DOI: 10.1080/14740338.2020.1832990. View

Zhang X, Xiang Q, Zhao X, Ma L, Cui Y . Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta-analysis. J Clin Pharm Ther. 2018; 44(2):163-173. DOI: 10.1111/jcpt.12780. View

Kane J, Carson W, Saha A, McQuade R, Ingenito G, Zimbroff D . Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002; 63(9):763-71. DOI: 10.4088/jcp.v63n0903. View

Hori H, Yoshimura R, Katsuki A, Hayashi K, Ikenouchi-Sugita A, Umene-Nakano W . The cognitive profile of aripiprazole differs from that of other atypical antipsychotics in schizophrenia patients. J Psychiatr Res. 2012; 46(6):757-61. DOI: 10.1016/j.jpsychires.2012.02.013. View

Li W, Zhang H, Wang Y, Zhang L, Ungvari G, Cheung T . Poor Insight in Schizophrenia Patients in China: a Meta-Analysis of Observational Studies. Psychiatr Q. 2020; 91(4):1017-1031. DOI: 10.1007/s11126-020-09786-7. View

Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F . Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013; 382(9896):951-62. DOI: 10.1016/S0140-6736(13)60733-3. View

Takeuchi H, Takekita Y, Hori H, Oya K, Miura I, Hashimoto N . Pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first-episode schizophrenia: Japanese Society of Clinical Neuropsychopharmacology treatment algorithms. Hum Psychopharmacol. 2021; 36(6):e2804. PMC: 8596443. DOI: 10.1002/hup.2804. View

Grunder G, Fellows C, Janouschek H, Veselinovic T, Boy C, Brocheler A . Brain and plasma pharmacokinetics of aripiprazole in patients with schizophrenia: an [18F]fallypride PET study. Am J Psychiatry. 2008; 165(8):988-95. DOI: 10.1176/appi.ajp.2008.07101574. View

10.

Mauri M, Paletta S, Di Pace C, Reggiori A, Cirnigliaro G, Valli I . Clinical Pharmacokinetics of Atypical Antipsychotics: An Update. Clin Pharmacokinet. 2018; 57(12):1493-1528. DOI: 10.1007/s40262-018-0664-3. View

11.

Tuplin E, Holahan M . Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity. Curr Neuropharmacol. 2017; 15(8):1192-1207. PMC: 5725548. DOI: 10.2174/1570159X15666170413115754. View

12.

Rekhi G, Tay J, Lee J . Impact of drug-induced Parkinsonism and tardive dyskinesia on health-related quality of life in schizophrenia. J Psychopharmacol. 2022; 36(2):183-190. DOI: 10.1177/02698811211055812. View

13.

Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N . Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019; 394(10202):939-951. PMC: 6891890. DOI: 10.1016/S0140-6736(19)31135-3. View

14.

De Raykeer R, Hoertel N, Blanco C, Lavaud P, Kaladjian A, Blumenstock Y . Effects of depression and cognitive impairment on quality of life in older adults with schizophrenia spectrum disorder: Results from a multicenter study. J Affect Disord. 2019; 256:164-175. DOI: 10.1016/j.jad.2019.05.063. View

15.

Mace S, Taylor D . Aripiprazole: dose-response relationship in schizophrenia and schizoaffective disorder. CNS Drugs. 2009; 23(9):773-80. DOI: 10.2165/11310820-000000000-00000. View

16.

Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M . The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry. 2004; 37(6):243-65. DOI: 10.1055/s-2004-832687. View

17.

Leucht S, Crippa A, Siafis S, Patel M, Orsini N, Davis J . Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia. Am J Psychiatry. 2019; 177(4):342-353. DOI: 10.1176/appi.ajp.2019.19010034. View

18.

Cutler A, Marcus R, Hardy S, ODonnell A, Carson W, McQuade R . The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia. CNS Spectr. 2006; 11(9):691-702. DOI: 10.1017/s1092852900014784. View

19.

Swainston Harrison T, Perry C . Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs. 2004; 64(15):1715-36. DOI: 10.2165/00003495-200464150-00010. View

20.

Mallikaarjun S, Kane J, Bricmont P, McQuade R, Carson W, Sanchez R . Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: an open-label, parallel-arm, multiple-dose study. Schizophr Res. 2013; 150(1):281-8. DOI: 10.1016/j.schres.2013.06.041. View